Preservation of the body cell mass is a major goal of nutritional therapy. Methods for assuring this preservation have primarily depended on the mass action of hyperalimentation, either oral or parenterally. The objective of this investigation is to determine optimal protein sparing during periods of negative caloric balance. Recognizing the importance of adequate fat mobilization and the favorable effect of starvation ketosis, investigation of the use of amino acid infusates free of glucose will be further studied. In this state, mobilization of endogenous fat stores must be a primary concern. We have developed the rationale which recognizes that the anabolic effect of insulin on protein metabolism is desirable but the anabolic effect of insulin on lipid metabolism is potentially harmful during starvation. Due to the relative sensitivity of muscle and adipose tissue to insulin, it is possible to exert an anabolic effect on muscle protein synthesis while reducing the risk of insulin interfering with fat mobilization. Further, during the acute phase of injury the stress response including catecholamines and glucocorticoids are so effective in meeting the metabolic demands, no benefit is possible from exogenous infusates of amino acids, carbohydrate or fat when compared with total starvation in injury. In sepsis, however, the beneficial effect to catecholamines is blocked, allowing hyperinsulinism and lowered free fatty acid levels. Thus, decreased lipolysis occurs. It is possible that special solutions containing branched chain amino acids or their keto analogues may palliate this pathological state. The success of our initial studies in over 500 patients utilizing this new therapy requires further investigation into the effectiveness, safety and indication. The influence of this nutritional support on cellular immunity, humoral immunity and phagocytosis will be identified.